Project Summary The goal of this research program is to develop stereoselective and regioselective alkene carbofunctionalization methods to enable efficient and sustainable organic syntheses. A major challenge in pharmaceutical synthesis is the catalytic construction of chiral molecules. Alkenes are versatile functional groups. 1,2-Dicarbofunctionalization and hydroalkylation of alkenes have emerged as compelling strategies to rapidly increase molecular complexity, but intermolecular asymmetric methods have not yet been developed for simple alkenes. The research projects described in this proposal address these synthetic challenges by developing a series of enantioselective reductive 1,2-dicarbofunctionalization and branch-selective hydroalkylation reactions of a broad scope of alkenes. These new methods would enable efficient routes to access target molecules with complex substitution patterns while introducing stereocenters. Catalyst development is built on the hypothesis that Ni-mediated radical addition to alkenes could result in new stereo-determining steps, such as radical capture or reductive elimination. Systematic mechanistic studies will be carried out to build stereochemical models, and insight gained will help overcome the limitations encountered in expanding the scope and utility of the new methods. Preliminary results showing new reactivity and verifying mechanistic proposals provide compelling evidence for the feasibility of this research. The expected outcomes of this research are as follows: (1) The development of stereoselective and regioselective reductive carbofunctionalization reactions of alkenes will allow for efficient access to vicinal disubstitution patterns and tertiary carbon centers, and thus novel retrosynthetic disconnections of pharmaceutical molecules; (2) The insight gained from mechanistic studies of model reactions and catalysts will not only facilitate the rational design of catalysts for the reactions described in this proposal, but also provide a guideline for understanding Ni-catalyzed coupling reactions more broadly.